6533b824fe1ef96bd1280233

RESEARCH PRODUCT

Dual role of interleukin-1alpha in delayed-type hypersensitivity and airway hyperresponsiveness.

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<i>Background:</i> Using a T helper (Th)1/Th2 disease model, we previously showed that genetically determined Th development depends on dendritic cell-derived interleukin (IL)-1α. In <i>Leishmania major</i> infections, Th1 immunity develops if IL-1α is present during T cell priming, whereas at later time points, IL-1α worsens disease outcome. In the present study, we determined the role of IL-1α in other Th2-mediated diseases. <i>Methods:</i> BALB/c mice were subjected to delayed-type hypersensitivity (DTH) or ovalbumin (OVA)/alum-induced allergic asthma in the presence or absence of IL-1α. <i>Results:</i> In DTH, mice treated with IL-1α during sensitization with keyhole limpet hemocyanin (KLH)/alum developed decreased footpad swelling associated with elevated KLH-specific interferon-γ levels. In asthma, significantly decreased airway hypersensitivity responses (AHRs) were detected upon treatment with IL-1α during T cell priming. In contrast to control mice, IL-1α-treated mice showed reduced peribronchial inflammatory infiltrates. The bronchoalveolar lavage (BAL) fluid contained significantly decreased eosinophil numbers (approximately 50%), but 4 times more neutrophils. The BAL fluid of IL-1α-treated BALB/c exhibited reduced amounts of IL-5 and OVA-specific IgE serum levels. In contrast, IL-1α treatment at later time points after sensitization or during allergen challenge worsened AHR, had no effect on lung inflammation and BAL fluid cell composition. Furthermore, cytokine levels (IL-5, IL-13) and antigen-specific IgE were increased or unaltered under these conditions. <i>Conclusion:</i> Similarly to leishmaniasis, IL-1α administration during sensitization of Th2-mediated allergic reactions suppresses the course of disease by shifting the immune response towards Th1, whereas later treatments worsen disease outcome. Future studies will elucidate the therapeutic value of IL-1α in asthmatic patients.